title: Kidney intragraft donor-specific antibodies as determinant of antibody-mediated lesions and poor graft outcome.
abstract: Allograft pathology, antibody-tissue interaction as demonstrated by C4d deposition and serological evidence of donor-specific antibodies (DSA) are the cardinal diagnostic features of antibody-mediated lesions (AML) in kidney transplantation. However, discrepancy between histological and serological findings is common, and more reliable diagnostic tools are called for. Here, we asked whether the in situ detection of DSA could serve as marker for AML. To that end, we applied the anti-HLA single antigen flow bead assay to eluates from 51 needle core graft biopsies performed for cause. Intragraft antibody profiles were correlated to serum DSA (sDSA), histological data and transplant outcome. The prevalence and the mean number of intragraft DSA (gDSA) were lower than that of sDSA (15/51 gDSA+ vs. 37/51 sDSA+ patients; 1.64 gDSA vs. 2.24 sDSA per patient). DSA were detected in all anti-HLA antibody-positive biopsies (15/15). The presence of gDSA was significantly associated with (1) microcirculation lesions taken individually (g, cg) and analyzed in functional clusters (ptc + g + cg > 0, cg + mm > 0), (2) C4d positivity and (3) a worse short-term transplant outcome (p = 0.05). These associations were not found for patients presenting only sDSA. Taken together, these results indicate that gDSA is a severity marker of antibody-mediated pathogenic process.
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, CHU Bordeaux, Bordeaux, France; Laboratory of Immunology and Immunogenetics, CHU Bordeaux, Bordeaux, France; UMR 5164, CNRS and University Bordeaux Segalen, Bordeaux, France.
authors.forename: T
authors.initials: T
authors.lastname: Bachelet
authors.forename: L
authors.initials: L
authors.lastname: Couzi
authors.forename: S
authors.initials: S
authors.lastname: Lepreux
authors.forename: M
authors.initials: M
authors.lastname: Legeret
authors.forename: G
authors.initials: G
authors.lastname: Pariscoat
authors.forename: G
authors.initials: G
authors.lastname: Guidicelli
authors.forename: P
authors.initials: P
authors.lastname: Merville
authors.forename: J-L
authors.initials: JL
authors.lastname: Taupin
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D007674:Kidney Diseases / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: Anti-HLA antibodies; antibody-mediated lesions; donor-specific antibodies; graft elution; kidney transplantation